This phase II trial examines the ability to test the molecular profile of patients with intrahepatic cholangiocarcinoma that can be removed by surgery (resectable) and assesses the safety and tolerability of preoperative chemotherapy (nab-paclitaxel, cisplatin, and gemcitabine) with or without targeted therapy (infigratinib) in this patient population. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side effects and work better than other forms of paclitaxel. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill cancer cells. Infigratinib is in a class of medications called kinase inhibitors and a form of targeted therapy that blocks the action of abnormal proteins called FGFRs that signal cancer cells to multiply. This helps stop or slow the spread of cancer cells. Giving chemotherapy with nab-paclitaxel, cisplatin, and gemcitabine and/or targeted therapy with infigratinib before surgery may make the tumor smaller for resection and may help prevent the cancer from coming back. Patients whose molecular profiling test result show a genetic change called FGFR2 fusion, receive both chemotherapy and targeted therapy while patients without a FGFR2 fusion just receive chemotherapy. Giving targeted therapy based on molecular profile test results prior to attempted resection for patients with intrahepatic cholangiocarcinoma that has a risk for either not being able to be removed or for coming back after it has been removed may help improve treatment outcomes in this patient population.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT05514912.
PRIMARY OBJECTIVE:
I. To assess the feasibility of a novel treatment strategy that includes conducting next generation sequencing (NGS)-based treatment on a preoperative tissue biopsy and subsequent administration of infigratinib phosphate (infigratinib) to patients with FGFR2 fusions versus neoadjuvant chemotherapy consisting of gemcitabine hydrochloride (gemcitabine), cisplatin, and nab-paclitaxel to all other patients for resectable intrahepatic cholangiocarcinoma.
SECONDARY OBJECTIVES:
I. To evaluate the efficacy of the intervention by assessing the radiological response rate.
II. To assess degree of pathologic response in the surgical specimen.
III. To assess response to therapy by measuring circulating tumor deoxyribonucleic acid (CT-DNA).
IV. To determine the R0 resection rate.
V. To determine recurrence-free survival (RFS).
VI. To determine overall survival (OS).
OUTLINE:
While awaiting NGS molecular profiling results, all patients receive nab-paclitaxel intravenously (IV) over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine IV over 30 minutes on days 1 and 8 of one 21-day cycle in the absence of disease progression or unacceptable toxicity.
After obtaining NGS molecular profiling results, patients who are FGFR2 fusion/translocation positive are assigned to Arm A, while patients who are FGFR2 fusion/translocation negative are assigned to Arm B.
ARM A: Patients receive infigratinib orally (PO) once daily (QD) on days 1-21 of each cycle. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients whose cancer is stable or improved undergo surgery to remove the tumor within 8 weeks of completing preoperative therapy per standard of care.
ARM B: Patients continue receiving nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine IV over 30 minutes on days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients whose cancer is stable or improved undergo surgery to remove the tumor within 8 weeks of completing preoperative therapy per standard of care.
After completion of study treatment, patients are followed up within 4 weeks and every 4 months for 3 years.
Lead OrganizationEmory University Hospital/Winship Cancer Institute
Principal InvestigatorShishir Kumar Maithel
